883-P: Effects of YG1699 and Sotagliflozin on Blood Glucose and Urinary Glucose Excretion in SD Rats

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Background and Aims: YG1699, a dual inhibitor of SGLT1 and SGLT2, recently showed greater glucose lowering than dapagliflozin in patients with type 1 diabetes. This study examined the potential mechanism of glucose reduction in rats. Materials and methods: Sprague Dawley rats received either 0.3, 1, 3, or 10mg/kg of YG1699, or 3, 10mg/kg of LX4211 (sotagliflozin), or vehicle by oral gavage (n=8 per group). Fifteen minutes later, 2g/kg glucose was orally administered, and blood glucose was measured at 0, 20, 40, 60, 90, 120, and 150 mins. The area under the curve (AUC) for glucose over time was calculated. In the urinary glucose excretion (UGE) test, 24-hour urine samples were collected after vehicle, 1, 3, or 10mg/kg doses of YG1699, or 3mg/kg sotagliflozin (n=5 per group). Differences between groups were evaluated by ANOVA. Results (See Table 1): 1, 3, and 10mg/kg doses of YG1699 and 3and 10mg/kg of sotagliflozin reduced glucose AUC and increased UGE compared to vehicle. Conclusion: Significant reductions in post-prandial glucose with YG1699 and sotagliflozin are associated with increased UGE. Glucose AUC after 10mg/kg YG1699 was less than 50% of vehicle. Disclosure J.Li: None. R.W.Xu: Consultant; Youngene Therapeutics. J.He: None. P.Lapuerta: Board Member; 4M Therapeutics, Consultant; Youngene Therapeutics, ViaCyte, Inc., Encuragen, Capsida, Provention Bio, Inc., Decibel Therapeutics, Crinetics, Next Phase Therapeutics.

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